Phloroglucinol Derivatives Exert Anti-Inflammatory Effects and Attenuate Cognitive Impairment in LPS-Induced Mouse Model.

Neuroinflammation is an inflammatory immune response that arises in the central nervous system. It is one of the primary causes of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Phloroglucinol (PG) is a natural product contained in extracts of plant, algae and microbe and has been reported to have antioxidant and anti-inflammatory properties. In this study, we synthesized PG derivatives to enhance antioxidant and anti-inflammatory activity. Among PG derivatives, 6 a suppressed pro-oxidative and inflammatory molecule nitric oxide (NO) production more effectively than PG. Moreover, 6 a dose-dependently reduced the expression of proinflammatory cytokines such as IL-6, IL-1ß, TNF-α, and NO producing enzyme iNOS in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Additionally, we confirmed that 6 a alleviated cognitive impairment and glial activation in mouse model of LPS-induced neuroinflammation. These findings suggest that novel PG derivative, 6 a, is a potential treatment for neurodegenerative diseases.

Prediction of postoperative cerebral infarction after combined bypass surgery in adult moyamoya disease: combining quantitative parameters on RAPID perfusion CT with clinically related factors.

OBJECTIVE: The aim of this study was to identify predictive factors of postoperative cerebral infarction (PostCI) following combined bypass (CB) surgery in adult patients with moyamoya disease (MMD) using quantitative parameters from the rapid processing of perfusion and diffusion (RAPID) perfusion CT (PCT) software. METHODS: The authors retrospectively reviewed 276 total hemispheres in patients with MMD who underwent CB. Preoperative volumes of time-to-maximum (Tmax) > 4 sec and > 6 sec were obtained from the RAPID analysis of PCT. These quantitative parameters, along with other clinical and angiographic factors, were statistically analyzed to determine the significant predictors for PostCI following CB. RESULTS: PostCI occurred in 17 hemispheres (6.16%). PCA involvement (p = 0.016), and the volume of Tmax > 6 sec (p < 0.001) and Tmax > 4 sec (p < 0.001), were identified as variables related to PostCI in the univariable analysis. In the multivariable analysis, the volume of Tmax > 6 sec (OR 1.013, 95% confidence interval 1.007-1.019, p < 0.001) was determined to be an independent predictive factor significantly associated with PostCI after CB in adult patients with MMD. In the receiver operating characteristic (ROC) curve, the cutoff value of the preoperative volume of Tmax > 6 sec was determined to be 59.5 ml (sensitivity 82.4%, specificity 71.9%, area under the ROC curve 0.811). CONCLUSIONS: For adult patients with MMD and a large volume of Tmax > 6 sec over 59.5 ml, more caution is required when deciding to undergo bypass surgery and in postoperative management.

Oxidized LDL Accelerates CartilageDestruction and Inflammatory Chondrocyte Death in Osteoarthritis by Disrupting the TFEB-Regulated Autophagy-Lysosome Pathway

Osteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes.

Differences in Clinical Outcomes Between Hydroxyurea-Resistant and -Intolerant Polycythemia Vera Patients

Background@#Previous studies have suggested that patients with polycythemia vera (PV) who exhibit hydroxyurea-resistance (HU-R) and -intolerance (HU-I) may have distinct characteristics and clinical outcomes. However, to date, no studies have reported a comparison between these two groups or assessed prognostic factors in these patients. @*Methods@#The objective of this study was to evaluate clinical outcomes and identify prognostic factors among PV patients with HU-R or HU-I. We conducted a review of PV patients who received frontline treatment with HU from nine centers and identified 90 patients with HU-R or HU-I. @*Results@#The cumulative incidence of thrombosis after 7 years of HU-R/I was 21.4%, and the incidence of disease progression was 22.5%. Comparing the HU-R and HU-I groups, the HU-R group had a significantly higher rate of disease progression (36.7% vs. 0.56%, P = 0.009), while there was no significant difference in thrombosis incidence (19.0% vs. 22.9%, P = 0.463). Multivariate analysis revealed that HU-R was an independent prognostic factor for progression-free survival (hazard ratio, 6.27, 95% confidence interval, 1.83–21.47, P = 0.003).Additionally, higher lactate dehydrogenase levels, multiple cardiovascular risk factors, and prior thrombosis were identified as unfavorable predictors of overall survival. @*Conclusion@#These findings suggest that patients with HU-R face a higher risk of hematological transformation, but have a comparable risk of thrombosis to patients with HU intolerance. These distinctions should guide decisions on second-line treatment options and clinical trials involving these patients.

Clinical Outcomes of Clipping and Coil Embolization for Ruptured Intracranial Aneurysms Categorized by Region and Hospital Size: A Nationwide Cohort Study in Korea

Background@#To analyze the outcomes of clipping and coiling for ruptured intracranial aneurysms (RIAs) based on data from the National Health Insurance Service in South Korea, with a focus on variations according to region and hospital size. @*Methods@#This study analyzed the one-year mortality rates for patients with RIAs who underwent clipping or coiling in 2018. Coiling was further categorized into non-stent assisted coiling (NSAC) and stent assisted coiling (SAC). Hospitals were classified as tertiary referral general hospitals (TRGHs), general hospitals (GHs), or semi-general hospitals (sGHs) based on size. South Korea’s administrative districts were divided into 15 regions for analysis. @*Results@#In 2018, there were 2,194 (33.1%) clipping procedures (TRGH, 985; GH, 827; sGH, 382) and 4,431 (66.9%) coiling procedures (TRGH, 1,642; GH, 2076; sGH, 713) performed for RIAs treatment. Among hospitals performing more than 20 treatments, the one-year mortality rates following clipping or coiling were 11.2% and 16.0%, respectively, with no significant difference observed. However, there was a significant difference in one-year mortality between NSAC and SAC (14.3% vs. 19.5%, P = 0.034), with clipping also showing significantly lower mortality compared to SAC (P = 0.019). No significant differences in other treatment modalities were observed according to hospital size, but clipping at TRGHs had significantly lower mortality than at GHs (P = 0.042). While no significant correlation was found between the number of treatments and outcomes at GHs, at TRGHs, a higher volume of clipping procedures was significantly associated with lower total mortality (P = 0.023) and mortality after clipping (P = 0.022). @*Conclusion@#Using Korea NHIS data, mortality rates for RIAs showed no significant variation by hospital size due to coiling’s prevalence. However, differences in clipping outcomes by hospital size and volume in TRGH highlight the need for national efforts to improve clipping skills and standardization. Additionally, the higher mortality rate with SAC emphasizes the importance of precise indications for its application.

Korean Nickel-Restricted Diet Based on Analysis of Nickel Content in Food Products / 대한피부과학회지

Background@#Nickel is a leading cause of allergic contact dermatitis. Patients with nickel allergy may suffer from persistent dermatitis not only through contact with nickel-plated items but also through ingestion of nickel-containing food. @*Objective@#This study aimed to evaluate the current nickel content in Korean food products and provide more up-to-date Korean nickel-restricted diets that would increase patient compliance. @*Methods@#The most frequently consumed food items were selected with replicates. Food samples were prepared according to the practices of normal consumers. The solid specimens were finely ground, and the liquid specimens were homogenized using a sterilized mixer. Tea bags were brewed in 100 mL of distilled water at 100 °C for 5 minutes. Solid (0.5 g) and liquid (2 g) specimens were subjected to microwave-assisted nitric acid digestion using inductively coupled plasma-mass spectrometry. @*Results@#In total, 147 samples were collected from different food categories, including plant-based products, animal-based products, packaged foods, and drinks. Cocoa powder had the highest concentration of nickel (1.56 mg/kg), which is consistent with the results of previous studies. Soy products such as fermented soybean paste (Doenjang) (1.16 mg/kg), fermented soybean with red chili paste (Ssamjang) (0.67 mg/kg), and tofu (0.37 mg/kg) had elevated concentration of nickel. Moreover, nut-derived products such as chocolate (1.10 mg/kg), ground coffee (0.86 mg/kg), almond (0.84 mg/kg), and peanuts (0.64 mg/kg) contained elevated nickel concentration. @*Conclusion@#The nickel content in food constantly changes depending on the food processing procedures and place of origin. Therefore, revising the nickel-restricted diet is necessary to enhance patients’ understanding of it and help reduce dietary nickel intake.

A Case of Nivolumab-Induced Bullous Pemphigoid in a Patient with Metastatic Breast Cancer / 대한피부과학회지

Nivolumab is a checkpoint inhibitor monoclonal antibody, designed to interact with the programmed death cell receptor-1, preventing the inhibitory signaling on cytotoxic T cells. Immune checkpoint inhibitors can lead to severe cutaneous immune-related adverse events (irAEs). A 54-year-old female with a breast cancer metastasis was referred to our clinic due to diffuse cutaneous lesions of crusted erythematous patches and multiple blisters for 2 weeks. Five months before presentation, she started nivolumab/eribulin immunotherapy. Skin biopsy showed subepidermal blistering with perivascular lymphohistiocytic infiltration with eosinophils. Direct immunofluorescence showed linear deposition of immunoglobulin G and C3 along the dermoepidermal junction, consistent with bullous pemphigoid.Temporal relationship between initiation of nivolumab and skin lesion suggested the diagnosis of nivolumab-induced bullous pemphigoid. Dermatologic toxicity is the most common irAEs associated with nivolumab, but nivolumab-induced bullous pemphigoid is rare. Given the widespread use of immunotherapy, it is important to document this case to develop proper management strategies.

Safety and Effectiveness of Passeo-18 Lux Drug-Coated Balloon Catheter in Infrainguinal Endovascular Revascularization in the Korean Population:A Multicenter Post-Market Surveillance Study

Objective@#To evaluate the safety and clinical outcomes of the Passeo-18 Lux drug-coated balloon (DCB) in endovascular revascularization procedures under real-world conditions in a Korean population with atherosclerotic disease of the infrainguinal arteries, including below-the-knee (BTK) arteries. @*Materials and Methods@#Eight institutions in the Republic of Korea participated in this prospective, multicenter, single-arm, post-market surveillance study. Two hundred patients with Rutherford class 2–5 peripheral arterial disease and infrainguinal lesions suitable for endovascular treatment were competitively enrolled. Data were collected at baseline, the time of intervention, discharge, and 1-, 6-, 12-, and 24-month follow-up visits. The primary safety endpoint was freedom from major adverse events (MAE) within 6 months (except when limiting the time frame for procedure- or device-related mortality to within 30 days), and the primary effectiveness endpoint was freedom from clinically driven target lesion revascularization (CDTLR) within 12 months after the procedure. @*Results@#A total of 197 patients with 332 target lesions were analyzed. Two-thirds of the patients had diabetes mellitus, and 41.6% had chronic limb-threatening ischemia. The median target lesion length was 100 mm (interquartile range: 56–133 mm).Of the target lesions, 35.2% were occlusions, and 14.8% were located in the BTK arteries. Rate of freedom from MAE was 97.9% at 6 months, and the rate of freedom from CD-TLR was 95.0% and 92.2% at 12 and 24 months, respectively. Subgroup analysis of 43 patients and 49 target lesions involving the BTK arteries showed rate of freedom from MAE of 92.8% at 6 months and rates of freedom from CD-TLR of 88.8% and 84.4% at 12 and 24 months, respectively. @*Conclusion@#The results of the present study, including the BTK subgroup analysis, showed outcomes comparable to those of other DCB studies, confirming the safety and effectiveness of Passeo-18 Lux DCB in the Korean population.

Psychometric Properties of the Insomnia Severity Index and Its Comparison With the Shortened Versions Among the General Population

Objective@#The aim of this study was to explore the psychometric properties of the Insomnia Severity Index (ISI) based on modern test theory, such as item response theory (IRT) and Rasch analysis, with shortened versions of the ISI among the general population. @*Methods@#We conducted two studies to evaluate the reliability and validity of the shortened versions of the ISI in a Korean population. In Study I, conducted via online survey, we performed an exploratory factor analysis (n=400). In Study II, confirmatory factor analysis (CFA) was conducted (n=400). IRT and Rasch analysis were performed on all samples. Participants symptoms were rated using the ISI, Dysfunctional Beliefs and Attitudes about Sleep–16 items, Dysfunctional Beliefs about Sleep–2 items, Patient Health Questionnaire–9 items, and discrepancy between desired time in bed and desired total sleep time. @*Results@#CFA showed a good fit for the 2-factor model of the ISI (comparative fit index=0.994, Tucker–Lewis index=0.990, root-meansquare-error of approximation=0.039, and standardized root-mean-square residual=0.046). The 3-item versions also showed a good fit for the model. All scales showed good internal consistency reliability. The scale information curve of the 2-item scale was similar to that of the full-scale ISI. The Rasch analysis outputs suggested a good model fit. @*Conclusion@#The shortened 2-factor ISI is a reliable and valid model for assessing the severity of insomnia in the Korean population. The results are needed to be explored further among the clinical sample of insomnia.

Nontuberculous mycobacterial infection in a sporotricoid distribution in Korea: a case report / 이화의대지

Nontuberculous mycobacterial infections, which are often acquired from environmental sources such as water and soil, exhibit a variety of cutaneous manifestations that frequently lead to misdiagnoses and delays in treatment. A 77-year-old woman presented with multiple skin lesions in a sporotricoid distribution on her right leg, which persisted despite standard antibiotic treatments. Based on the skin biopsy, revealing granulomatous inflammation with acid-fast bacilli, and PCR testing, a nontuberculous mycobacterial infection was diagnosed. Antimycobacterial drug combinations, including clarithromycin, isoniazid, and rifampicin for 4 months, complete the skin lesion's clearance. This case underscores the need for heightened suspicion and the use of appropriate diagnostic techniques, including tissue biopsies and molecular methods such as PCR.

Histologic features and predicting prognosis in ulcerative colitis patients with mild endoscopic activity

Background/Aims@#We aimed to evaluate the histologic features predictive of prognosis and correlate them with endoscopic findings in patients with ulcerative colitis (UC) having complete or partial mucosal healing (MH). @*Methods@#We prospectively collected and reviewed data from patients with UC who underwent colonoscopy or sigmoidoscopy with biopsy. Complete and partial MH were defined as Mayo endoscopic subscores (MESs) of 0 and 1, respectively. Histologic variables, including the Nancy index (NI), predicting disease progression (defined as the need for medication upgrade or hospitalization/surgery), were evaluated and correlated with endoscopic findings. @*Results@#Overall, 441 biopsy specimens were collected from 194 patients. The average follow-up duration was 14.7 ± 7.4 months. There were 49 (25.3%) and 68 (35.1%) patients with MESs of 0 and 1, respectively. Disease progression occurred only in patients with an MES of 1. NI ≥ 3 was significantly correlated with disease progression during follow-up. Mucosal friability on endoscopy was significantly correlated with NI ≥ 3 (61.1% in NI < 3 vs. 88.0% in NI ≥ 3; p = 0.013). @*Conclusions@#Histological activity can help predict the prognosis of patients with UC with mild endoscopic activity. Mucosal friability observed on endoscopy may reflect a more severe histological status, which can be a risk factor for disease progression.

Hair Cell Regeneration: From Animals to Humans

Cochlear hair cells convert sound into electrical signals that are relayed via the spiral ganglion neurons to the central auditory pathway. Hair cells are vulnerable to damage caused by excessive noise, aging, and ototoxic agents. Non-mammals can regenerate lost hair cells by mitotic regeneration and direct transdifferentiation of surrounding supporting cells. However, in mature mammals, damaged hair cells are not replaced, resulting in permanent hearing loss. Recent studies have uncovered mechanisms by which sensory organs in non-mammals and the neonatal mammalian cochlea regenerate hair cells, and outlined possible mechanisms why this ability declines rapidly with age in mammals. Here, we review similarities and differences between avian, zebrafish, and mammalian hair cell regeneration. Moreover, we discuss advances and limitations of hair cell regeneration in the mature cochlea and their potential applications to human hearing loss.

Development and validation of a prediction model for evaluating extubation readiness in preterm infants.

Successful early extubation has advantages not only in terms of short-term respiratory morbidities and survival but also in terms of long-term neurodevelopmental outcomes in preterm infants. However, no consensus exists regarding the optimal protocol or guidelines for extubation readiness in preterm infants. Therefore, the decision to extubate preterm infants was almost entirely at the attending physician's discretion. We identified robust and quantitative predictors of success or failure of the first planned extubation attempt before 36 weeks of post-menstrual age in preterm infants (<32 weeks gestational age) and developed a prediction model for evaluating extubation readiness using these predictors. Extubation success was defined as the absence of reintubation within 72 h after extubation. This observational cohort study used data from preterm infants admitted to the neonatal intensive care unit of Seoul National University Bundang Hospital in South Korea between July 2003 and June 2019 to identify predictors and develop and test a predictive model for extubation readiness. Data from preterm infants included in the Medical Informative Medicine for Intensive Care (MIMIC-III) database between 2001 and 2008 were used for external validation. From a machine learning model using predictors such as demographics, periodic vital signs, ventilator settings, and respiratory indices, the area under the receiver operating characteristic curve and average precision of our model were 0.805 (95% confidence interval [CI], 0.802-0.809) and 0.917, respectively in the internal validation and 0.715 (95% CI, 0.713-0.717) and 0.838, respectively in the external validation. Our prediction model (NExt-Predictor) demonstrated high performance in assessing extubation readiness in both internal and external validations.

Improved Muscle Mass and Function With Protein Supplementation in Older Adults With Sarcopenia: A Meta-Analysis

Objective@#To systematically review the effects of protein supplementation in older adults with sarcopenia. @*Methods@#A systematic literature search was conducted in PubMed, Cochrane Library, and Embase databases until May 2023. The inclusion criteria were as follows: (1) randomized controlled trials with a quantitative study design; (2) studies with a study group of older adults with sarcopenia; (3) studies comparing muscle mass, muscle strength, and performance of older adults with sarcopenia after protein supplementation; and (4) studies published up to May 2023. @*Results@#Six retrospective comparative studies, including 715 patients, met the inclusion criteria. The nutritional supplementation group exhibited significant improvement in appendicular skeletal muscle mass (standardized mean difference [SMD]=0.41; 95% confidence interval [CI], 0.24–0.58; p<0.001; I2=1%), while handgrip strength (SMD=0.37; 95% CI, -0.32–1.07; p=0.29; I2=94%) and Short Physical Performance Battery (SPPB) (SMD=0.35; 95% CI, -0.47–1.18; p=0.40; I2=94%) showed a tendency for improvement. @*Conclusion@#Nutritional supplementation with protein increased appendicular muscle mass in older adults with sarcopenia and improved handgrip strength and SPPB scores.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Survey About Specific Clinical Scenarios (Version 2023.1)

Background@#During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period. @*Methods@#The KSNO Guideline Working Group consisted of 22 multidisciplinary experts on neuro-oncology in Korea. In order to confirm a consensus reached by the experts, opinions on 5 specific clinical scenarios about the management of brain tumor patients during the crisis period were devised and asked. To build-up the consensus process, Delphi method was employed. @*Results@#The summary of the final consensus from each scenario are as follows. For patients with newly diagnosed astrocytoma with isocitrate dehydrogenase (IDH)-mutant and oligodendroglioma with IDH-mutant/1p19q codeleted, observation was preferred for patients with low-risk, World Health Organization (WHO) grade 2, and Karnofsky Performance Scale (KPS) ≥60, while adjuvant radiotherapy alone was preferred for patients with high-risk, WHO grade 2, and KPS ≥60. For newly diagnosed patients with glioblastoma, the most preferred adjuvant treatment strategy after surgery was radiotherapy plus temozolomide except for patients aged ≥70 years with KPS of 60 and unmethylated MGMT promoters. In patients with symptomatic brain metastasis, the preferred treatment differed according to the number of brain metastasis and performance status. For patients with newly diagnosed atypical meningioma, adjuvant radiation was deferred in patients with older age, poor performance status, complete resection, or low mitotic count. @*Conclusion@#It is imperative that proper medical care for brain tumor patients be sustained and provided, even during the crisis period. The findings of this consensus survey will be a useful reference in determining appropriate treatment options for brain tumor patients in the specific clinical scenarios covered by the survey during the future crisis.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Recommendation Using the Delphi Method (Version 2023.1)

Background@#During the coronavirus disease 2019 (COVID-19) pandemic, the need for appropriate treatment guidelines for patients with brain tumors was indispensable due to the lack and limitations of medical resources. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. @*Methods@#The KSNO Guideline Working Group was composed of 22 multidisciplinary experts on neuro-oncology in Korea. In order to reach consensus among the experts, the Delphi method was used to build up the final recommendations. @*Results@#All participating experts completed the series of surveys, and the results of final survey were used to draft the current consensus recommendations. Priority levels of surgery and radiotherapy during crises were proposed using appropriate time window-based criteria for management outcome. The highest priority for surgery is assigned to patients who are life-threatening or have a risk of significant impact on a patient’s prognosis unless immediate intervention is given within 24–48 hours. As for the radiotherapy, patients who are at risk of compromising their overall survival or neurological status within 4–6 weeks are assigned to the highest priority. Curative-intent chemotherapy has the highest priority, followed by neoadjuvant/adjuvant and palliative chemotherapy during a crisis period. Telemedicine should be actively considered as a management tool for brain tumor patients during the mass infection crises such as the COVID-19 pandemic. @*Conclusion@#It is crucial that adequate medical care for patients with brain tumors is maintained and provided, even during times of crisis. This guideline will serve as a valuable resource, assisting in the delivery of treatment to brain tumor patients in the event of any future crisis.

Intensified First Cycle of Rituximab Plus Eight Cycles of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone with Rituximab Chemotherapy for Advanced-Stage or Bulky Diffuse Large B-Cell Lymphoma: A Multicenter Phase II Consortium for Improving Survival of Lymphoma (CISL) Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). @*Materials and Methods@#Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. @*Results@#Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). @*Conclusion@#Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Outcomes of Endoscopic Tympanoplasty for Large Perforations: A Multicenter Retrospective Study in South Korea

Objectives@#. Endoscopic tympanoplasty (ET) provides minimally invasive transcanal access to the middle ear and improves middle ear visibility for the treatment of tympanic membrane (TM) perforations. However, the literature on surgical outcomes for large TM perforations is lacking and limited to small series. This study aimed to evaluate the clinical benefits of ET for large TM perforations. @*Methods@#. This retrospective cohort study was conducted at nine tertiary referral hospitals in South Korea, where 252 patients who underwent ET as primary surgery from September 2019 to August 2021 were included. The outcome measures included the graft success rate and pre- and postoperative audiometric data. @*Results@#. In 239 patients, the graft success rate of ET for large or subtotal perforations was 86.2% (206 patients), while the graft failure rate was 13.8% (33 patients). The graft failure rate was directly correlated with surgical techniques, including overlay and medial or lateral underlay tympanoplasty (P=0.027). Lateral underlay tympanoplasty showed the most favorable results. Sex, laterality, etiology, site and size of perforation, operation time, and graft materials did not vary significantly between the graft success and failure groups (P>0.05). The mean air-bone gap (ABG) improved significantly in both groups (graft success group: 10.0±0.6 dB and graft failure group: 7.7±0.3 dB; P<0.001). However, the ABG improvement did not significantly differ between the groups. Analysis of covariance revealed that the postoperative 500-Hz bone conduction threshold improved after successful ET (adjusted coefficient, –11.351; 95% confidence interval, –21.491 to –1.212; P=0.028). @*Conclusion@#. This study involved the largest population to date of large TM perforations treated by ET. The study findings suggest that ET is feasible and effective in treating large TM perforations.

Comparison between Placement of an Amniotic Membrane Contact Lens and Temporary Amniotic Membrane Transplantation

Purpose@#We compared the clinical utilities of an amniotic contact lens and temporary amniotic membrane transplantation in patients with persistent corneal epithelial defects. @*Methods@#Patients diagnosed with persistent corneal epithelial defects from November 2019 to July 2022 were randomly assigned to either lens placement for 2 weeks or temporary transplantation for 1 week, and the outcomes were retrospectively analyzed. The best-corrected visual acuity, corneal sensation, tear film break-up time, and corneal opacity were measured before and after the interventions. The treatment success rates, recurrences, and other complications were analyzed during the follow-up period. @*Results@#We placed lenses in 32 patients (32 eyes) and 20 patients (20 eyes) underwent transplantation. In both groups, significant differences in best-corrected visual acuity, corneal sensation, tear film break-up time, and corneal opacity were apparent after intervention vs. before. None of the parameters showed any significant differences in terms of their rates of change. @*Conclusions@#In patients with persistent corneal epithelial defects, amniotic contact lens placement is an effective outpatient procedure and is not inferior to temporary amniotic membrane transplantation.

The Impact of Slow Infusion Intermittent Feeding on Gavage Feeding-Associated Cardiorespiratory Deterioration in Neonatal Intensive Care Unit Infants

Purpose@#Infants in the neonatal intensive care unit (NICU) often show cardiorespiratory deterioration during gavage feeding. We aimed to determine whether slow infusion intermittent feeding (SIIF) can reduce respiratory deterioration during gavage feeding in preterm infants in the NICU. @*Methods@#Data on preterm infants whose gavage feeding method was changed to SIIF (1-­­hour infusion with an infusion pump and 2-­hour rest within a 3­-hour interval) from bolus gravity feeding (2-­ or 3-­hour interval) due to feeding­-associated cardiorespiratory deterioration were retrospectively reviewed. A significant cardiorespiratory event was defined as a saturation level below 80% or heart rate below 80 bpm. We compared the frequency of cardiorespiratory events and the level of respiratory support 24 hours before and after the application of SIIF. @*Results@#A total of 34 infants were enrolled and analyzed. The total frequency of desaturation or bradycardia significantly decreased after SIIF application (8.94 vs. 5.03, P=0.001). The frequency of feeding-­related bradycardia and desaturation also significantly decreased (4.15 vs. 1.68, P=0.008). Out of 34 patients, 11 (32.4%) had a decreased level of ventilator support within 1 day after SIIF. The respiratory severity scores of the 10 patients who received invasive ventilator support decreased significantly after SIIF (5.24 vs. 4.59, P=0.032). @*Conclusion@#SIIF significantly decreased gavage feeding­-associated cardiorespiratory events and reduced respiratory support in approximately one-­third of subjects. Therefore, SIIF may be a therapeutic option for gavage feed-­associated respiratory deterioration in preterm infants in the NICU.